Diaphyseal Dysplasias
Osteogenesis Imperfecta
A connective tissue disorder characterised by osteoporosis, fragile bones, dentinogenesis imperfecta, deafness, blue sclera, ligamentous hyper mobility, herniae and they bruise easily.
Classification (Sillence 1981)
- Congenita (recessive)
- Tarda (dominant)
|
Type |
Qualifying Suffixes |
Inheritance |
Clinically |
|
I A&B (1/30,000) |
Congenita (tarda) |
Autosomal dominant |
Dentinogenesis imperfecta may be a feature (Types A without & B with) |
|
II (1/62,000) |
Congenita |
Autosomal recessive |
Blue sclera |
|
III (Rare) |
Congenita (tarda) |
Autosomal recessive |
Sclera bluish at birth but normalises |
|
IV A&B (Rare) |
Congenita (tarda) |
Autosomal dominant |
Dentinogenesis imperfecta may be a feature (Types A without & B with) |
Clinically
- Dependant on type and severity
- Short stature, limb deformities and broad skull
- May have blue sclera, scoliosis, ligament laxity and tendency to bruise easily
- Coxa vara, bowing of the femur and tibia, knock knees, valgus feet and dislocation of the radial head are all fairly common
X-Rays
- Typically multiple fractures of various age
- Angular deformities and bent bones
- If severe, multiple rib fractures may limit respiration
- Defective subperiosteal bone formation makes thin bone with normal width of physis
- Popcorn calcifications evident in metaphysis resolve after skeletal maturity
Wormianbones
- Detached portions of the primary ossification centres of the adjacent membrane bones
- Should be more than 10 to be significant, and should measure 6 mm x 4 mm, arranged in a mosaic pattern (Claus Wormius, Danish anatomist)
- Also seen in Cleido-cranial dysplasia, Pyknodysostosis, Hypophosphatasia and Hypothyroidism
- Vertebrae initially bi-concave, then develop wedge fractures
- Scoliosis develops in about 40%
- Osteoporosis and feathering of trabeculae in milder forms
- Erlenmeyer flask appearance in some and trumpet in others
- Coxa vara and acetabular dysplasia is common
- Basilar invagination into base of skull may occur
- Hyperplastic callus formation may occur and mimic appearance of osteogenic sarcoma (M > F and sclera is white)
Pathology
- Defective Type I collagen maturation beyond reticulin fibre stage, associated with defective cross linking
- Single gene disorders that affect the structure and biosynthesis of Type 1 collagen, give rise to a varieties of Osteogenesis Imperfecta
- More than 70 mutations in the genes that encode the chains of Type 1 collagen have been identified
- Mild phenotypes may blend with common disorders such as osteoporosis
- Histologically bone is characterised by larger areas of osseous tissue devoid of organised trabecular or lamellar pattern, with the bone being much more characteristic of woven or primitive bone
- Osteoblasts have normal or increased activity, but fail to produce or organise collagen
- Affects both enchondral and membranous bone formation
- Osteoclasts are normal and increased in number
- The physis is usually broad and irregular
- Secondary ossification centres show delayed maturation
- Fractures heal at the normal rate, but with abnormal bone
- Blue sclera is caused by the thinness of the collagen layer
- Changes occur in the skin, ligaments, tendons, sclera and inner ear
- Associated with numerous other congenital malformations, particularly cardiac and hip anomalies
- Dentinogenesisimperfecta : enamel of the lamina dura is relatively normal, but the teeth have an amber, yellowish-brown or translucent bluish-gray colour because of improper deposition of dentine
Laboratory tests
- Serum calcium and phosphorus are normal
- Alkaline phosphatase may be increased
Differential Diagnosis
- Hypophosphatasia (low alkaline phosphatase in serum)
- Achondroplasia (no increased bone fragility)
Treatment
- No specific treatment
- Aim to provide and maintain function
- Splint fractures with minimal immobilisation
- Intra-medullary fixation can be used
- Plaster immobilisation for fractures carries the added disadvantage that osteoporosis is increased and it is possible to enter into a vicious circle
- Associated with difficult anaesthesia, due to :
- Small size of thorax and poor respiratory function
- Larger size of the tongue relative to the jaw
- Small body size
- Small blood volume
Prognosis
- Congenital severe forms die in utero or soon after birth
- Few live through puberty
- Milder forms may have a near normal life expectancy
Type I
Inheritance
Autosomal dominant
Incidence
- 1 / 30,000 (commonest type)
- Age at diagnosis birth to early childhood
Classification
- IA : No dentinogenesis imperfecta
- IB : Dentinogenesis imperfecta
Clinical Features
- Osteoporosis, abnormal bone fragility
- Distinctly blue sclera throughout life
- Presenile hearing loss affects about 40%; need hearing aids (otosclerosis or nerve compression)
- In 10% fractures present at birth, rest in infancy or childhood
- Short stature of postnatal onset, usually falling between 2 and 3 standard deviations below the mean
- Joint hyperlaxity and skeletal deformities
- About 20% of the adults in this group have kypho-scoliosis and in the remainder there is progressive loss of height resulting from platyspondyly and kyphosis
Type II
Inheritance
Autosomal recessive
Incidence
1 / 62,000
Clinical Features
- Blue sclera
- Extreme bone fragility
- Often intra-uterine death
- Born with multiple bony deformities
- Facial appearance is typical with marked lack of ossification of the whole cranial vault, which consists of numerous small plates of bone
Prognosis
Death in perinatal period or early infancy (intracranial haemorrhage)
Type III
Inheritance
Autosomal recessive
Incidence
- Extremely rare
- Age at diagnosis evident at birth or early infancy
Clinical Features
- Bluish sclera at birth, but becomes less blue with age
- Severe bone fragility
- Deformity of long bones, skull and spine
- Present congenitally or in early infancy with fractures
- The smallest of all patients with OI, if survive
- High childhood mortality and further mortality in the third decade, because of complications of severe kypho-scoliosis
- Codfish flattening of vertebrae
Prognosis
- May survive into adult life
- Death often due to the complications of severe scoliosis
Type IV
Inheritance
Autosomal dominant
Incidence
Rare
Classification
- IVA : No dentinogenesis imperfecta
- IVB : Dentinogenesis imperfecta
Clinical Features
- Normal sclera or if bluish at birth becomes normal
- Bone fragility of varying severity
- Hearing impairment less common than in Type I
- Difficult to differentiate from Type III
Progressive diaphyseal dysplasia (Engelmann’s disease)
Inheritance
Autosomal dominant
Incidence
- Rare, less than 1 / million
- Age at diagnosis 1-2 years
- Male more than Female
Clinical Features
- Wasting of muscles and weakness
- Presents with delayed walking or running
- Also pain or weakness of affected limbs
- Delayed puberty and hypogonadism
- Dry hard skin, dental caries, ocular proptosis, anaemia and hepatosplenomegally may develop
X-Rays
- Fusiform swelling / expansion of diaphysis of long bones
- Affects middle 1/3 and spreads proximally and distally
- Cortical surface becomes irregular
- Medullary canal becomes almost obliterated
Laboratory tests
- Alkaline phosphatase and urinary hyroxyproline may be increased
- Hypocalcaemia and hyperphosphataemia
- Positive calcium balance may be present
Differential Diagnosis
- Polyostotic fibrous dysplasia
- Multiple enchondromatosis
- Juvenile Pagets
- Heavy metal poisoning
- Ewings sarcoma
Treatment
- No specific treatment
- NSAIDs may help pain
- Steroids may help if NSAIDs fail
Craniodiaphyseal dysplasia
Clinical Features
- Mental retardation
- Cranial nerve palsies
- Diaphysis of long bones thickened and irregular
X-Ray
Thickening of skull and long bone diaphysis
Pathology
Progressive thickening of all parts of the skull
Prognosis
Main problems are neurosurgical and maxillo-facial